A 23-Year-Old Man with Leptospirosis and Acute Abdominal Pain

A 23-year-old Man with Leptospirosis and Acute Abdominal Pain

Momal Mazhar MD; Janet J. Kao MD; and Dennis Thomas Bolger Jr. MD, MPH

Abstract Case Report Leptospirosis is a zoonosis caused by the spirochete Leptospira interrogans. A 23-year-old Caucasian man from the continental United States Most cases of leptospirosis are mild to moderate, and self-limited. The course residing in Hawai‘i presented to the emergency department of disease, however, may be complicated by multiorgan dysfunction such as in Weil’s disease. We present a case of Weil’s disease with pancreatitis (ED) three days prior to admission with a two-day history of in a young Caucasian man residing in Hawai‘i. Although leptospirosis is fever (104F/40C), chills, headache, neck stiffness, productive common in Hawai‘i, few patients present with pancreatitis. This report of cough, nausea, and diffuse myalgias. At that time, he denied leptospirosis-induced pancreatitis should help raise awareness of clinicians photophobia, rash, abdominal pain, and diarrhea. On exam, to assess for pancreatitis when evaluating a patient with leptospirosis and he was found to be tachycardic (119 beats per minute [bpm]) acute abdominal pain. and febrile (101.4F/38.5C). He received 2 L normal saline. He was reassessed and found to be hemodynamically stable. Keywords He was discharged by the ED physician with prescriptions for Leptospirosis, Weil’s disease, pancreatitis, multiorgan dysfunction, acetaminophen and ondansetron. The patient reported that his hyperbilirubinemia, acute abdominal pain fever was controlled with acetaminophen, however, his nausea was unremitting. Introduction Two days after his first ED visit, the patient developed symp- Leptospirosis is a zoonosis caused by the spirochete Leptospira toms of photophobia, non-bloody, watery stools, non-bloody, interrogans. Compared to temperate regions, the incidence of non-bilious emesis up to seven times per day, bloody sputum, this disease is significantly higher in tropical and subtropical 1 and dark tea-colored urine. On the night prior to his second ED regions. In the United States, an estimated 100-200 lepto- visit, the patient also noticed yellowing of his eyes and face and spirosis cases are identified annually, of which 50% occur in 2 onset of abdominal pain prompting him to return to the ED. Hawai‘i. The infection is primarily transmitted to humans The patient reported swimming in freshwater 2 weeks prior to through direct contact with water, mud, or soil contaminated 3 admission, but denied skin abrasions and water ingestion. He with the urine of chronically infected mammals and rodents. An further denied history of recent travel, sick contacts, eating incubation period of 5-14 days is typical. During this time, the uncooked foods, animal bites, and positive purified protein spirochetes proliferate in the bloodstream and then disseminate derivative (PPD) status. Upon questioning, the patient admit- hematogenously. The clinical manifestations of leptospirosis in ted to recreational alcohol consumption, his last episode being humans vary from a subclinical infection to severe illness with consumption of 4 beers (48 fluid ounces) twelve days prior to multiorgan dysfunction. Usual disease presentation includes a onset of illness. flu-like illness with mild hepatic and renal impairment, whereas severe disease forms are characterized by hepatorenal failure, encephalopathy, and pulmonary hemorrhage.4-6 The illness itself has a biphasic nature: an initial septicemia phase and consequent immune phase. During septicemia, patients will present with fever, headache, myalgia, conjunctival suffusion, and various non-specific findings such as mild cough, Abbreviations rash, lymphadenopathy, nausea, and vomiting.7 Subsequently, ALT: alanine aminotransferase patients may have a brief afebrile period of variable duration AST: aspartate aminotransferase whereafter they develop organ derangements, most commonly bpm: beats per minute of the liver and kidneys. In rare cases, it is reported to directly CDC: Center for Disease Control CT: Computerized tomography affect other organs such as the eye, bone marrow, and pancreas. ED: Emergency Department Weil’s disease, the most severe form of illness, is character- ICU: Intensive Care Unit ized by jaundice, renal failure, and hemorrhage with a variable IgM: Immunoglobulin M 4 INR: International Normalized Ratio clinical course. Infected patients with acute renal failure may PPD: Purified Protein Derivative demonstrate elevated serum amylase levels, however, clinical PT: Prothrombin Time symptoms of pancreatitis are uncommon.4 We present a case PTT: Partial Thromboplastin Time of Weil’s disease accompanied by pancreatitis.

HAWAI‘I JOURNAL OF MEDICINE & PUBLIC HEALTH, OCTOBER 2016, VOL 75, NO 10 291 Upon admission, the patient’s vital signs were significant for transferase (AST) were elevated (184 mEq/L and 144 mEq/L, hypertension (149/81 mmHg), tachycardia (120 bpm), pyrexia respectively), and there was significant hyperbilirubinemia (101.1F/38.4C), and tachypnea (24 breaths per minute); he also (total 13.0 mEq/L, direct 9.9 mEq/L, indirect 3.1 mEq/L). demonstrated pulse oximetry of 94% on room air, and BMI 22 Coagulation studies demonstrated prothrombin time (PT) 13.2 kg/m2. In addition, he was icteric, with conjunctival injection seconds, partial thromboplastin time (PTT) 28.9 seconds, and but no suffusion. He had decreased breath sounds bilaterally, international normalized ratio (INR) of 1.0. Urinalysis revealed abdominal rigidity, and arthralgias of his hips, knees, and large amounts of blood and bilirubin. Troponin I was not el- ankles, but no effusions. Kernig’s and Brudzinski’s signs were evated. Computed tomography (CT) scan of the chest (Figure absent. On abdominal exam, bowel sounds were hyperactive. 1) revealed diffuse, bilateral peribronchial thickening and Abdominal organomegaly could not be assessed because the consolidation with extensive bud nodular opacities. Abdominal patient had severe rigidity and tenderness to palpation and ultrasound was performed and did not demonstrate gallblad- percussion. There was no rebound tenderness. der inflammation, common bile duct dilatation, or evidence of Laboratory studies demonstrated leukocytosis (approximately gallstones. CT scan of the abdomen was performed without 18,000/mm3) with neutrophil predominance (83%), thrombocy- oral or intravenous contrast, due to the patient’s acute kidney topenia (42,000/mm3), hyponatremia (132 mEq/L), hypokalemia injury, and demonstrated hepatosplenomegaly without biliary (3.0 mEq/L), respiratory acidosis, metabolic alkalosis, and wide dilatation and an unremarkable pancreas. anion gap acidosis, as well as acute kidney injury (creatinine The patient was admitted for systemic inflammatory response levels 4.4 mg/dL). Total creatine kinase was elevated (1162 syndrome with suspicion for infection or inflammation in the IU/ml), alanine aminotransferase (ALT) and aspartate amino- hepatobiliary system. Differential diagnoses included chol-

Figure 1. Computed tomography (CT) scan of the chest demonstrating diffuse, bilateral peribronchial thickening and consolidation with extensive bud nodular opacities.

HAWAI‘I JOURNAL OF MEDICINE & PUBLIC HEALTH, OCTOBER 2016, VOL 75, NO 10 292 angitis, pancreatitis, hepatitis (viral, autoimmune, drug- or has been related to toll-like receptor (TLR) activation from toxin-associated), leptospirosis, dengue, murine typhus, and Leptospira lipoproteins.4,5 Cardiac involvement may present typhoid fever. As such, he was started on empiric intravenous with non-specific electrocardiogram abnormalities or findings antibiotics (doxycycline, ceftriaxone, and metronidazole) while consisting with pericarditis or myocarditis (PR interval prolon- awaiting blood/sputum/urine/stool cultures, gram stains, and gation, T-wave inversion, first degree atrioventricular block).4 serological test results. Acute renal failure, also associated with TLR activation, is Shortly after admission to the medical floor, the patient reported in 16%-40% of cases where oliguria is a significant developed respiratory distress. He was found to have oxygen predictor of death.4,9 saturation of 80% on room air. He was tachycardic, tachypneic, Although acute pancreatitis has been recognized as a rare and expectorated a large volume of blood. The patient quickly involvement of the multiorgan dysfunction of leptospirosis, became less responsive to verbal stimuli. Given his acute respi- most reported cases are of patients who developed hemor- ratory failure, the patient was transferred to the intensive care rhagic or necrotizing pancreatitis several days after the onset unit (ICU) where he was supported with supplemental high flow of disease. Furthermore, most reports deal with leptospirosis oxygen via Venturi mask and close monitoring. At this time, the cases occurring in under-developed countries and involving patient’s serum lipase was found to be 1750 Units/Liter (normal mainly elderly patients.10-13 The case presented herein adds to range 13-60 U/L). The patient became increasingly lethargic the body of knowledge in that leptospirosis-induced pancreatitis and he was unable to tolerate oral intake. The patient’s condi- occurred in a young patient and at the early onset of disease. This tion slowly improved with intravenous fluids and empiric triple patient developed acute abdominal pain and rigidity coupled antibiotic therapy. He was weaned to supplemental oxygen via with high lipase level and inadequate pancreatic imaging. nasal cannula and had no further respiratory distress or evidence He became critically ill from a combination of acute kidney of recurrent pulmonary hemorrhage. injury, acute respiratory failure, pancreatitis, acute cholestatic Back on the hospitalist ward team, the patient demonstrated hepatitis, and immune dysfunction. In the context of this report, jaundice, decreased abdominal rigidity, and tenderness to palpa- it is important to consider alcohol consumption as a possible tion predominantly in the right upper quadrant and epigastric cause of pancreatitis. However, the patient reported last inges- region. Laboratory values demonstrated down-trending hepatic tion 12 days prior to disease onset, decreasing the likelihood of transaminases, serum creatinine, and creatine kinase. However, alcohol-induced pancreatitis. Also, patients often minimize the serum bilirubin levels were increased (total 18.7 mEq/L, direct amount consumed. Animal studies suggest alcohol consumption 16.5 mEq/L, indirect 2.2 mEq/L). Abdominal ultrasound was is usually not associated with pancreatitis unless 5 drinks or repeated and showed an unremarkable pancreas and gallblad- more per day (60 g of ethanol) are consumed.14 Nonetheless, der, but demonstrated hepatomegaly without evidence of biliary such results suggest that ethanol could sensitize the pancreas to dilatation or ascites. The patient was started on a clear liquid injury while additional factors may trigger the development of diet and continued to demonstrate nausea and epigastric pain overt pancreatitis. In the setting of leptospirosis, this may be Lep- without emesis. Serological tests returned significant only for tospira antigen-associated vascular endothelial damage, which leptospira immunoglobulin M (IgM). The Center for Disease has been associated with the various other organ dysfunctions Control (CDC) would define a positive leptospira IgM as a of leptospirosis.4 Vascular injury most likely causes ischemic probable case. The patient’s antibiotics were narrowed to intra- effects on the pancreas such as through decreased removal venous doxycycline. The patient was discharged after demon- of reactive oxygen species, intracellular enzymes and toxins, strating clinical improvement on completion of seven-days of and increased stasis of injurious elements that, together, may intravenous doxycycline. At the time of discharge, the patient manifest as acute pancreatitis. Leptospira interrogans-induced was able to tolerate a regular diet without nausea. The patient acute pancreatitis seems rare. However, because of the high was educated that his illness was likely related to freshwater mortality rate associated with pancreatitis, clinicians should exposure to the infectious agent and counseled on methods for keep in mind the possibility of Leptospira-induced pancreatitis decreasing risk. when confronted with leptospirosis.15

Discussion Conclusions Leptospirosis is a disease with a variable grade of severity and Leptospirosis is a frequently encountered infectious disease organ involvement. Neurologic injury is seen in up to 25% in Hawai‘i and certain other parts of the world. Weil’s disease of all cases and is most commonly associated with aseptic represents the most severe form of leptospirosis. While multi- meningitis; however, intracranial hemorrhages, cerebellitis, organ dysfunction is common, pancreatitis is rare. Furthermore, and myelitis have been reported as well.4,8 Hepatic injury is significant alcohol consumption may predispose leptospirosis associated with disruption of cellular cohesion, plugging of bile patients to pancreatitis. Acute pancreatitis is associated with canaliculi, and occasional acute inflammatory infiltrates.4 This significant morbidity and mortality, resulting in the death of pathophysiology is consistent with the laboratory findings of 20% of patients.16 Thus, it is essential to assess risk factors for hypertransaminemia, and direct hyperbilirubinemia. Pulmonary pancreatitis, such as alcohol consumption and gallstones, in injury often presents with hemorrhage, as in our patient, and patients presenting with leptospirosis.

HAWAI‘I JOURNAL OF MEDICINE & PUBLIC HEALTH, OCTOBER 2016, VOL 75, NO 10 293 Conflict of Interest 6. Yew KL, Go CS, Razali F. Pancreatitis and myopericarditis complication in leptospirosis infection. Journal of the Formosan Medical Association. 2014.doi: 10.1016/j.jfma.2014.01.021 None of the authors identify any conflict of interest. 7. Bal AM. Unusual clinical manifestations of leptospirosis. Journal of Postgraduate Medicine. 2005;51(3):179-183. Authors’ Affiliation: 8. Vale TC, Santos GC, Santurnino SF, et al. Weil syndrome: a rare cause of cerebral venous - John A. Burns School of Medicine, University of Hawai‘i, Honolulu, HI thrombosis. JAMA Neurol. 2014;71(2):238-239. 9. Chakrabarti A, Nandy M, Pal D, Mallik S. A rare case of Weil’s disease with alveolar hemorrhage. Asian Pac J Trop Biomed. 2014;4(Suppl 1):S66-S69. Available at http://www.ncbi.nlm.nih.gov/ Correspondence to: pmc/articles/PMC4025278/. Accessed December 28, 2014. Dennis Thomas Bolger Jr. MD, MPH; Department of Medicine, 10. Popa D, Vasile D, Ilco A. Severe acute pancreatitis - a serious complication of leptospirosis. J John A. Burns School of Medicine, University of Hawai‘i, 1356 Lusitana Street #702, Med Life. 2013;6(3):307-309. Honolulu, HI, 96813; Email: [email protected] 11. Boonpucknavig V, Douangchawee G, Niwattaykul K. Infectious diseases and tropic disease pathology: SY16-2A pathology of leptospirosis: autopsy study. Pathology. 2014;46(Suppl 2):S27. Available at http://journals.lww.com/pathologyrcpa/pages/articleviewer.aspx?year=2014&issu References e=10002&article=00092&type=abstract. Accessed December 28, 2014. 1. Togal T, Sener A, Yucel N, Demirbilek S, Akgun FS, Aydogan M, Ucar M, Ersoy MO. Intensive 12. Jain AKC, Mohan LN. Acute necrotising pancreatitis associated with leptospirosis - a case care of a Weil’s disease with multiorgan failure. J Clin Med Res. 2010;2(3):145-149. report. Indian J Surg. 2013;75(3):245-246. 2. Centers for Disease Control and Prevention. (2015). Leptospirosis. Retrieved from http://www. 13. Silva AP, Burg LB, Locatelli JFS, Manes J, Crispim M. Leptospirosis presenting as ascend- cdc.gov/leptospirosis/health_care_workers/. ing progressive leg weakness and complicating with acute pancreatitis. Braz J Infect Dis. 3. Panicker JN, Mammachan R, Jayakumar RV. Primary neuroleptospirosis. Postgrad Med J. 2011;15(5):493-497. 2001;77(911):589-590. 14. Clemens DL, Wells MA, Schneider KJ, Singh S. Molecular mechanisms of alcohol associated 4. Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, Levett PN, Gilman RH, pancreatitis. World J Gastrointest Pathophysiol. 2014;5(3):147-157. Willig MR, Gotuzzo E, Vinetz JM. Leptospirosis: a zoonotic disease of global importance. Lancet 15. Bakker OJ, van Brunschot S, van Santvoort HC, et al. Early versus on-demand nasoenteric Infect Dis. 2003;3(12):757-771. tube feeding in acute pancreatitis. N Engl J Med. 2014;371(21):1983-1993. 5. Panagopoulos P, Terzi I, Karanikas M, Galanopoulos N, Maltezos E. Myocarditis, pancreatitis, 16. Kong L, Santiago N, Han TQ, Zhang SD. Clinical characteristics and prognostic factors of polyarthritis, mononeuritis multiplex and vasculitis with symmetrical peripheral gangrene of severe acute pancreatitis. World J Gastroenterol. 2004;10(22):3336-3338. the lower extremities as a rare presentation of leptospirosis: a case report and review of the literature. J Med Case Report. 2014;8(150). Available at http://www.jmedicalcasereports.com/ content/8/1/150. Accessed December 28, 2014.

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